Under pathological conditions in the middle ear, such as secretory otitis media (SOM), muco-exudates produced by the muco-ciliary system may accumulate instead of clear through the Eustachian tube. This study is concerned with the factors which govern mucosal secretions and their clearance by ciliary propulsion from the middle ear cavity. In earlier research we have established that for proper clearance by ciliary action mucus must have the character of an incipient gel and that it is normally secreted as such; systems which are sols or very stiff gels are not transported. Mucus undergoes spontaneous structural changes since it is not normally a permanently crosslinked system. Under conditions of high CO2 content, such as occur in SOM ears, there is a shift towards an increased number of mucus producing cells. It has also been shown that the muco-ciliary system of the Eustachian tube in SOM ears is functional. Hence clearance can be linked to the number of cells producing mucus, the amount produced, the rheological character of the secretion and its time course on the epithelium. The immediate objectives of this project are to characterize the features of the glycoprotein macromolecular aggregates from which mucus derives its special rheological properties and determine the factors linking molecular structure, rheological response and transportability on the epithelium. The approach involves: structural characterization of the glycoprotein entity, before and after disulphide bond breakage, by fingerprinting the sugar side chains and determining their location and the location of the -S-S-bridges; structure, distribution of crosslinks and rheology of intact mucus by permeation and viscoelastic characterization; transport function by performance on the depleted frog palate; the mechanics of transmission of ciliary beat by optical means and the factors controlling mucus production, cell differentiation and ciliary function by organ and tissue culture under a variety of environmental conditions. Routine middle ear gas pressure and composition measurements coupled with data obtained on pathological mucus are to be correlated with information from our fundamental studies to arrive at an improved understanding and treatment of clearance malfunction in SOM.